A 31-year-old man presenting with an 18-month history of sexual dysfunction resulting from severe adult-onset IHH (LH U/L, FSH U/L, T nmol/L). Initial therapy with 50 mg of clomiphene citrate (CC) three times a day for 7 days, with overnight LH pulse profiling and 9 am T levels evaluated at baseline and on completion. A 2-month washout period, followed by low-dose maintenance therapy (25-50 mg/d) for 4 months.
MAIN OUTCOME MEASURE(S):Baseline and stimulated T levels and LH pulsatility; effect on sexual function.
RESULT(S):Clomiphene therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. CONCLUSION(S):Isolated hypogonadotropic hypogonadism may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. On theoretical grounds, reversal of gonadotropin deficiency with CC might be expected to have a similar biological effect.

In a 2011 randomized controlled study, researchers recruited 54 healthy men whose mean 25(OH)D levels were in the deficiency range for a year-long intervention. They divided the subjects into two groups. The first group of 23 men had an average serum 25(OH)D of nmol/L and took a daily placebo. The second group of 31 men had an average serum 25(OH)D of nmol/L and took a daily 3332-IU vitamin D supplement. After the trial was finished, the researchers observed a significant increase in total testosterone from nmol/L to nmol/L in the supplement group. 19 In contrast, there were hardly any changes in testosterone concentrations in the placebo group. 19 These findings suggest that men deficient in vitamin D who take a proper vitamin D supplement may fix low levels of low testosterone.